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Biomedical subjects

M Carlson

Publications and source records attributed to M Carlson.

At least 55 records · Page 3Linked to original sources

Catheter ablation of accessory pathways, atrioventricular nodal reentrant tachycardia, and the atrioventricular junction: final results of a prospective, multicenter clinical trial. The Atakr Multicenter Investigators Group.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of a temperature-controlled radiofrequency catheter ablation system. METHODS AND RESULTS: The patient population included 1050 patients who had undergone ablation of atrioventricular nodal reentrant tachycardia (AVNRT), an accessory pathway (AP), or the atrioventricular junction (AVJ). Ablation was successful in 996 patients. The probability of success was highest among patients who had undergone ablation of the AVJ, lowest in patients who had undergone ablation of an AP, and in between for patients who had undergone ablation of AVNRT. A major complication occurred in 32 patients. Four variables predicted ablation success (AVJ, AVNRT, or left free wall AP ablation and an experienced center). Four factors predicted arrhythmia recurrence (right free wall, posteroseptal, septal, and multiple APs). Two variables predicted development of a complication (structural heart disease and the presence of multiple targets), and 3 variables predicted an increased risk of death (heart disease, lower ejection fraction, and AVJ ablation). CONCLUSIONS: These findings may serve as a guide to clinicians considering therapeutic options in patients who are candidates for ablation.

Adolescent↗

Glucose repression in yeast.

The Snf1 protein kinase is a central component of the signaling pathway for glucose repression in yeast. Recent studies have addressed the regulation of Snf1 kinase activity and elucidated mechanisms by which Snf1 controls repression and activation of glucose-repressed genes. Important advances include evidence that Snf1 regulates the localization of the Mig1 repressor and that Snf1 functions at multiple points to control Cat8 and Sip4, the activators of gluconeogenic genes.

Gene Expression Regulation, Enzymologic↗

Increased intraluminal release of eosinophil granule proteins EPO, ECP, EPX, and cytokines in ulcerative colitis and proctitis in segmental perfusion.

OBJECTIVE: The role of the eosinophil granulocyte in bowel mucosa in inflammatory bowel disease still remains obscure. The present study was performed in order to elucidate the local eosinophil activity and activating cytokines in the inflamed lesions of colon and rectum in patients with ulcerative colitis and proctitis. METHODS: The activity of intestinal eosinophils with respect to the release of granule proteins was studied in 18 patients (10 with colitis and 8 with isolated proctitis) and 18 healthy controls, using intraluminal segmental perfusion of the sigmoid colon and rectum. The released amounts of eosinophil granule proteins: eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil protein X (EPX) to perfusion fluid were determined by radioimmunoassays. The intraluminal release of possible eosinophil priming cytokines granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 8 (IL-8), were analyzed by immunoassays. RESULTS: The mucosal release of ECP, EPO, and EPX was increased 10- to 20-fold in patients with colitis and proctitis compared with controls. The intraluminal release of GM-CSF and IL-8, was several-fold enhanced in patients with colitis and proctitis. We also found a correlation between all three eosinophil granule proteins and the levels of IL-8/GM-CSF in the sigmoidal segments of patients with colitis. CONCLUSIONS: We conclude that the increased release of ECP, EPO, and EPX to colorectal perfusion fluid indicate eosinophil involvement in the local disease in patients with colitis and proctitis. IL-8 and GM-CSF may play a role in eosinophil accumulation and priming in colitis.

Adult↗

Psychometric properties of a Chinese translation of the SF-36 health survey questionnaire in the Well Elderly Study.

OBJECTIVES: To evaluate the psychometric properties of a Chinese translation of the 36-item Short Form Health Survey (SF-36) in the Well Elderly Study--a randomized clinical trial designed to evaluate the effectiveness of preventive occupational therapy services specifically tailored for multiethnic, independent-living, older adults. METHODS: Translation and back-translation procedures were used to obtain appropriate meanings for the SF-36 survey questions and to ensure face, functional, and conceptual equivalence. RESULTS: Statistical analyses demonstrated satisfactory reliability and validity, with the results generally similar to those reported for older Anglo adults. DISCUSSION: As the percentage of older adults of diverse ethnicity increases, the need for health care research and service strategies that can effectively include multiple ethnicities becomes paramount. The results of this study suggest that a Chinese-translated SF-36 can be used to assess multiple dimensions of health in a Mandarin-speaking population of older adults.

Aged↗

Sip4, a Snf1 kinase-dependent transcriptional activator, binds to the carbon source-responsive element of gluconeogenic genes.

The carbon source-responsive element (CSRE) mediates transcriptional activation of the gluconeogenic genes during growth of the yeast Saccharomyces cerevisiae on non-fermentable carbon sources. Previous studies have suggested that the Cat8 protein activates the expression of CSRE-binding factors. We show here that one of these factors is Sip4, a glucose-regulated C6 zinc cluster activator which was identified by its interaction with the Snf1 protein kinase. We present genetic evidence that Sip4 contributes to transcriptional activation by the CSRE and biochemical evidence that Sip4 binds to the CSRE. Binding was detected in electrophoretic mobility shift assays with both yeast nuclear extracts and a bacterially expressed Sip4 fusion protein. Evidence suggests that Sip4 also activates the expression of other CSRE-binding proteins. Finally, we show that Cat8 regulates SIP4 expression and that overexpression of Sip4 compensates for loss of Cat8. We propose a model for activation by the CSRE in which Sip4 and Cat8 have related functions, but Cat8 is the primary regulator because it controls Sip4 expression.

Basic-Leucine Zipper Transcription Factors↗

Srb/mediator proteins interact functionally and physically with transcriptional repressor Sfl1.

Srb/mediator proteins that are associated with RNA polymerase II holoenzyme have been implicated in transcriptional repression in Saccharomyces cerevisiae. We show here that the defect in repression of SUC2 caused by mutation of SRB8, SRB9, SRB11, SIN4 or ROX3 is suppressed by increased dosage of the SFL1 gene, and the genetic behavior of the sfl1Delta mutation provides further evidence for a functional relationship. Sfl1 acts on SUC2 through a repression site located immediately 5' to the TATA box, and Sfl1 binds this DNA sequence in vitro. Moreover, LexA-Sfl1 represses transcription of a reporter, and repression is reduced in an srb9 mutant. Finally, we show that Sfl1 co-immunoprecipitates from cell extracts with Srb9, Srb11, Sin4 and Rox3. We propose that Sfl1, when bound to its site, interacts with Srb/mediator proteins to inhibit transcription by RNA polymerase II holoenzyme.

Bacterial Proteins↗

Predictors of fluoroscopy time and estimated radiation exposure during radiofrequency catheter ablation procedures.

The objective of this study was to identify factors that predict fluoroscopy duration and radiation exposure during catheter ablation procedures. The patient population included 859 patients who participated in the Atakr Ablation System clinical trial at 1 of 9 centers (398 male and 461 female patients, aged 36 +/- 21 years). Each patient underwent catheter ablation of an accessory pathway, the atrioventricular junction, or atrioventricular nodal reentrant tachycardia using standard techniques. The duration of fluoroscopy was 53 +/- 50 minutes. Factors identified as independent predictors of fluoroscopy duration included patient age and sex, the success or failure of the ablation procedure, and the institution at which the ablation was performed. Catheter ablation in adults required longer fluoroscopy exposure than it did in children. Men required longer durations of fluoroscopy exposure than did women. The mean estimated "entrance" radiation dose was 1.3 +/- 1.3 Sv. The dose needed to cause radiation skin injury was exceeded during 22% of procedures. The overall mean effective absorbed dose from catheter ablation procedures was 0.025 Sv for female patients and 0.017 Sv for male patients. This degree of radiation exposure would result in an estimated 1,400 excess fatal malignancies in female patients and 2,600 excess fatal malignancies in male patients per 1 million patients.

Adolescent↗

Direct interaction between Rsc6 and Rsc8/Swh3,two proteins that are conserved in SWI/SNF-related complexes.

The RSC complex of Saccharomyces cerevisiae is closely related to the SWI/SNF complex. Both complexes are involved in remodeling chromatin structure and they share conserved components. The RSC proteins Sth1, Rsc8/Swh3, Sfh1 and Rsc6 are homologs of the SWI/SNF proteins Swi2/Snf2, Swi3, Snf5 and Swp73 respectively. To investigate the RSC complex, we isolated a temperature-sensitive swh3 allele. A screen for multicopy suppressors yielded plasmids carrying the RSC6 and MAK31 loci. RSC6 also suppressed the formamide sensitivity of a strain with a C-terminal truncation of SWH3 . We show that Swh3 and Rsc6 fusion proteins interact in the two-hybrid system and that the swh3-ts mutation impairs this interaction. Finally, bacterially produced Swh3 and Rsc6 fusion proteins interact in vitro , supporting the genetic evidence for direct interaction between Swh3 and Rsc6 in vivo . We have previously shown that Swh3 also interacts with Sth1. These findings, together with the conservation of these proteins in the SWI/SNF complex and in mammalian SWI/SNF-related complexes, strongly suggest that these proteins form a structural core for the complex.

Alleles↗

Glucose-regulated interaction of a regulatory subunit of protein phosphatase 1 with the Snf1 protein kinase in Saccharomyces cerevisiae.

The Snf1 protein kinase family has been conserved in eukaryotes. In the yeast Saccharomyces cerevisiae, Snf1 is essential for transcription of glucose-repressed genes in response to glucose starvation. The direct interaction between Snf1 and its activating subunit, Snf4, within the kinase complex is regulated by the glucose signal. Glucose inhibition of the Snf1-Snf4 interaction depends on protein phosphatase 1 and its targeting subunit, Reg1. Here we show that Reg1 interacts with the Snf1 catalytic domain in the two-hybrid system. This interaction increases in response to glucose limitation and requires the conserved threonine in the activation loop of the kinase, a putative phosphorylation site. The inhibitory effect of Reg1 appears to require the Snf1 regulatory domain because a reg1Delta mutation no longer relieves glucose repression of transcription when Snf1 function is provided by the isolated catalytic domain. Finally, we show that abolishing the Snf1 catalytic activity by mutation of the ATP-binding site causes elevated, constitutive interaction with Reg1, indicating that Snf1 negatively regulates its own interaction with Reg1. We propose a model in which protein phosphatase 1, targeted by Reg1, facilitates the conformational change of the kinase complex from its active state to the autoinhibited state.

Fungal Proteins↗

Cystic fibrosis through a female perspective: psychosocial issues and information concerning puberty and motherhood.

The purpose of the study was to investigate psychosocial issues concerning puberty and motherhood among CF adult females, to see how they had obtained and conceived information on these matters and how they would like information to be given. Fourteen adult CF females were interviewed. The majority of the women felt socially accepted and did not remember being ashamed over their delayed puberty. Thirteen of the women had been or were living in stable sexual relationships. However, the study revealed problems with destructive behaviour during puberty due to thoughts about premature death, secret worries over delayed puberty, poorly received information about puberty and fertility, avoidance of close relationships with the opposite sex during adolescence and concerns about being a mother with a chronic illness. Information about puberty and fertility should be given individually and in small discussion groups with teenage girls combined with thorough medical and psychological guidance concerning motherhood.

Adolescent↗

Regulation of glucose utilization in yeast.

Our understanding of the regulatory mechanisms controlling the glucose response in yeast has advanced in the past year. Two transporter-like proteins have been shown to function as glucose sensors in a pathway for glucose induction of transporter genes. Our understanding of the glucose repression mechanism has been augmented by studies of the Snf1 protein kinase, the Mig1 repressor, and the role of Snf1 in inhibiting Mig1 and regulating activators. DNA microarrays have been used to assess glucose-regulated gene expression.

DNA, Fungal↗

Snf1 protein kinase regulates phosphorylation of the Mig1 repressor in Saccharomyces cerevisiae.

In glucose-grown cells, the Mig1 DNA-binding protein recruits the Ssn6-Tup1 corepressor to glucose-repressed promoters in the yeast Saccharomyces cerevisiae. Previous work showed that Mig1 is differentially phosphorylated in response to glucose. Here we examine the role of Mig1 in regulating repression and the role of the Snf1 protein kinase in regulating Mig1 function. Immunoblot analysis of Mig1 protein from a snf1 mutant showed that Snf1 is required for the phosphorylation of Mig1; moreover, hxk2 and reg1 mutations, which relieve glucose inhibition of Snf1, correspondingly affect phosphorylation of Mig1. We show that Snf1 and Mig1 interact in the two-hybrid system and also coimmunoprecipitate from cell extracts, indicating that the two proteins interact in vivo. In immune complex assays of Snf1, coprecipitating Mig1 is phosphorylated in a Snf1-dependent reaction. Mutation of four putative Snf1 recognition sites in Mig1 eliminated most of the differential phosphorylation of Mig1 in response to glucose in vivo and improved the two-hybrid interaction with Snf1. These studies, together with previous genetic findings, indicate that the Snf1 protein kinase regulates phosphorylation of Mig1 in response to glucose.

Bacterial Proteins↗

Functional relationships of Srb10-Srb11 kinase, carboxy-terminal domain kinase CTDK-I, and transcriptional corepressor Ssn6-Tup1.

The Srb10-Srb11 protein kinase of Saccharomyces cerevisiae is a cyclin-dependent kinase (cdk)-cyclin pair which has been found associated with the carboxy-terminal domain (CTD) of RNA polymerase II holoenzyme forms. Previous genetic findings implicated the Srb10-Srb11 kinase in transcriptional repression. Here we use synthetic promoters and LexA fusion proteins to test the requirement for Srb10-Srb11 in repression by Ssn6-Tup1, a global corepressor. We show that srb10delta and srb11delta mutations reduce repression by DNA-bound LexA-Ssn6 and LexA-Tup1. A point mutation in a conserved subdomain of the kinase similarly reduced repression, indicating that the catalytic activity is required. These findings establish a functional link between Ssn6-Tup1 and the Srb10-Srb11 kinase in vivo. We also explored the relationship between Srb10-Srb11 and CTD kinase I (CTDK-I), another member of the cdk-cyclin family that has been implicated in CTD phosphorylation. We show that mutation of CTK1, encoding the cdk subunit, causes defects in transcriptional repression by LexA-Tup1 and in transcriptional activation. Analysis of the mutant phenotypes and the genetic interactions of srb10delta and ctk1A suggests that the two kinases have related but distinct roles in transcriptional control. These genetic findings, together with previous biochemical evidence, suggest that one mechanism of repression by Ssn6-Tup1 involves functional interaction with RNA polymerase II holoenzyme.

Bacterial Proteins↗

The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell?

Mammalian AMP-activated protein kinase and yeast SNF1 protein kinase are the central components of kinase cascades that are highly conserved between animals, fungi, and plants. The AMP-activated protein kinase cascade acts as a metabolic sensor or "fuel gauge" that monitors cellular AMP and ATP levels because it is activated by increases in the AMP:ATP ratio. Once activated, the enzyme switches off ATP-consuming anabolic pathways and switches on ATP-producing catabolic pathways, such as fatty acid oxidation. The SNF1 complex in yeast is activated in response to the stress of glucose deprivation. In this case the intracellular signal or signals have not been identified; however, SNF1 activation is associated with depletion of ATP and elevation of AMP. The SNF1 complex acts primarily by inducing expression of genes required for catabolic pathways that generate glucose, probably by triggering phosphorylation of transcription factors. SNF1-related protein kinases in higher plants are likely to be involved in the response of plant cells to environmental and/or nutritional stress.

AMP-Activated Protein Kinases↗

Occupation in lifestyle redesign: the Well Elderly Study Occupational Therapy Program.

This article describes an innovative preventive occupational therapy intervention for well older adults, the Well Elderly Treatment Program. In a previously reported large-scale randomized effectiveness study, this intervention was found to be highly successful in enhancing the physical and mental health, occupational functioning, and life satisfaction of multicultural, community-dwelling elders. In this article, the philosophical background, manner of development, topical content, methods of program delivery, and mechanisms underlying the program's positive effects are discussed, along with implications for occupational therapy practice. The treatment was based on application of occupational science theory and research and emphasized the therapeutic process of lifestyle redesign in enabling the participants to actively and strategically select an individualized pattern of personally satisfying and health-promoting occupations. The wide-ranging effectiveness of the program supports the occupational therapy profession's emphasis on occupation in affecting health and positions practitioners to extend their services to the realm of preventive interventions.

Aged↗